Blood-Based Biomarkers for Neurological Disorders: From Simoa to Clinical Implementation
Advanced detection platforms including single-molecule arrays (Simoa), electrochemiluminescence, and mass spectrometry have enabled measurement of low-abundance neurological biomarkers in blood rather than CSF. Clinically, the Abeta42/Abeta40 ratio and pTau isoforms now aid Alzheimer's diagnosis, while GFAP and UCH-L1 help rule out mild traumatic brain injury. Despite these advances, challenges in assay standardisation, sensitivity-specificity trade-offs, and the need for longitudinal validation remain barriers to broad clinical deployment.
The original study
Advances in Circulating Biomarkers for Neurodegenerative Diseases, Traumatic Brain Injuries, and Central Nervous System Tumors.
- Authors
- Yang M, Zhang A, Chen M, Cao J
- Journal
- Annals of laboratory medicine
- Type
- Journal Article, Review
- PMID
- 40528459
Original abstract
Neurological disorders, including neurodegenerative diseases, traumatic brain injuries (TBI), and central nervous system (CNS) tumors, are complex conditions that significantly impact patients globally. Timely diagnosis and monitoring are critical for improving outcomes, driving the need for reliable biomarkers. Specifically, biomarkers detectable in cerebrospinal fluid (CSF) and blood offer important insights into disease presence and progression. This review explores the evolution of circulating blood biomarkers for neurodegenerative diseases, TBI, and CNS tumors, highlighting advanced detection technologies from enzyme-linked immunosorbent assays (ELISAs) to electrochemiluminescence (ECL) assays, single-molecule arrays (Simoa), and mass spectrometry. Advanced technologies with enhanced sensitivity and specificity, particularly in detecting low-abundance analytes, facilitate the investigation of CSF biomarkers for various neurological disorders. We also describe the progress in blood-based biomarkers for , emerging as less invasive alternatives to CSF sampling. Clinically, the implementation of Alzheimer's disease (AD) blood biomarkers Aβ42/Aβ40 ratio and Apolipoprotein E isoform-specific peptide can aid the diagnosis, while p-tau181 and p-tau217 differentiates AD dementia from non-AD neurodegenerative diseases. Blood glial fibrillary acidic protein and ubiquitin C-terminal hydrolase-L1 are used in ruling out mild TBI. Despite these innovations, challenges remain, including assay standardization, sensitivity/specificity trade-offs, and the requirement for longitudinal studies to understand biomarker utility over time. Future research should focus on addressing these challenges to fully realize the potential of blood-based biomarkers in neurological disorder diagnostics and patient care.